Search

Owing to its simplicity, selectivity, high yield, and the absence of byproducts, the "click" azide-alkyne reaction is widely used in many areas. The reaction is usually catalyzed by copper(I), which selectively produces the 1,4-disubstituted 1,2,3-triazole regioisomer. Ruthenium-based catalysts were later developed to selectively produce the opposite regioselectivity─the 1,5-disubstituted 1,2,3-triazole isomer. Ruthenium-based catalysis, however, remains only tested for click reactions in solution, and the suitability of ruthenium catalysts for surface-based click reactions remains unknown. Also unknown are the electrical properties of the 1,4- and 1,5-regioisomers, and to measure them, both isomers need to be assembled on the electrode surface. Here, we test whether ruthenium catalysts can be used to catalyze surface azide-alkyne reactions to produce 1,5-disubstituted 1,2,3-triazole, and compare their electrochemical properties, in terms of surface coverages and electron transfer kinetics, to those of the compound formed by copper catalysis, 1,4-disubstituted 1,2,3-triazole isomer. Results show that ruthenium(II) complexes catalyze the click reaction on surfaces yielding the 1,5-disubstituted isomer, but the rate of the reaction is remarkably slower than that of the copper-catalyzed reaction, and this is related to the size of the catalyst involved as an intermediate in the reaction. The electron transfer rate constant (

Refereed/Peer-reviewed Background: Current diagnostic methods for prostate cancer are invasive and lack specificity towards aggressive forms of the disease, which can lead to overtreatment. A new class of non-invasive alternatives is under development, in which urinary biomarkers are detected using biosensing devices to offer rapid and accurate prostate cancer diagnosis. These different approaches are systematically reviewed and their potential for translation to clinical practice is evaluated. Methods: A systematic review of the literature was performed in May 2021 using PubMed Medline database, Embase, and Web of Science. The objective was to review the structural designs and performance of biosensors tested on urine samples from patients with prostate cancer. Results: A total of 76 records were identified. After screening and eligibility, 14 articles were included and are discussed in this paper. The biosensors were discussed based on the target biomarkers and detection technologies used, as well as the results of the clinical studies. Most of the works reported good discrimination between patients with prostate cancer and controls. Conclusions: This review highlights the potential of urinary biosensors for non-invasive prostate cancer detection. However, clinical studies have so far only been conducted on small cohorts of patient, with large scale trials still needed to validate the proposed approaches. Overall, the consensus arising from the proof of concepts studies reviewed here, is that an adequate combination of biomarkers into multiplex biosensor platforms is required to achieve accurate diagnostic tests. Furthermore, whether such devices can discriminate between aggressive and indolent cancer has not yet been addressed, because it entails optimized biomarkers panels and long-term clinical trials.

Plasma-polymerized polyoxazoline (POx) thin films offer a fast, scalable, and solvent-free method of electrode functionalization through the unique chemistry of the oxazoline ring. However, for POx to be a viable green alternative to existing surface modification approaches, the films should be able to withstand the processing steps involved in biosensing. Here, the effects that current exposure, extended incubation, and repeated electrode rinses have on the electrochemical and physical stability of polymethyloxazoline thin films are investigated. The films are observed to become more diffusive after incubation and rinse steps. While no significant changes in chemistry were observed, a marked change in nanotopography occurred after exposure to current, suggesting a change in the polymer film structure. Refereed/Peer-reviewed

A proof on concept study was conducted in the quest for dual-functional surfaces that provide both biopassivity and bioactivity. It presents the development of a biopassive platform that readily binds to bioactive molecules via copper-catalyzed acetylene-azide cycloaddition reaction. Acetylene-decorated poly(2-methyl-2-oxazoline) (PMOXA) brushes were grafted on an Nb2O5 surface. This biopassive brush platform was then exposed to various azide-decorated compounds of different sizes (molecular weight) and chemical structure, i.e. benzyl, mannose, and antimicrobial peptide (AMP), to react through the cycloaddition reaction. The different nature of the compounds “clicked” to the brushes requires different strategies of characterization. Time of flight-secondary ion mass spectroscopy (ToF-SIMS) results showed that benzyl-triazole-characteristic fragments were successfully bound to the surface. Fluorescence spectroscopy results indicated that mannose-azide molecules tagged with dye-carrying Concanavalin A (Con-A) could bind to the PMOXA-acetylene brush via specific and, to some extent, nonspecific interactions. Similarly, optical waveguide light-mode spectroscopy (OWLS) and quartz crystal microbalance-dissipation (QCM-D) analysis showed a successful reaction between AMP-azide and the PMOXA-acetylene brush platform. Together, these results validated the original approach of generating dual-functional surfaces using a “click” reaction between oxazoline brushes and a variety of ligands relevant to a range of applications.

Hexaminolevulinate (HAL) induced Protoporphyrin IX (PpIX) fluorescence is commonly used to differentiate cancer cells from normal cells in vivo, as for instance in blue light cystoscopy for bladder cancer diagnosis. A detailed approach is here provided to use this diagnostic principle ex vivo in an immunosensor device, towards enabling non-invasive cancer diagnostic from body fluids, such as urine. Several factors susceptible to affect the applicability of HAL-assisted diagnosis in body fluids were tested. These included the cell viability and its impact on PpIX fluorescence, the storage condition and shelf life of HAL premix reagent, light exposure (360–450 nm wavelengths) and its corresponding effect on both intensity and bleaching of the PpIX fluorescence as a function of the microscopy imaging conditions. There was no significant decrease in the viability of bladder cancer cells after 6 h at 4 °C (student’s t-test: p > 0.05). The cellular PpIX fluorescence decreased in a time-dependent manner when cancer cells were kept at 4 °C for extended period of time, though this didn’t significantly reduce the fluorescence intensity contrast between cancer and non-cancer cells kept in the same condition for 6 h. HAL premix reagent kept in long term storage at 4 °C induced stronger PpIX fluorescence than reagent kept in the − 20 °C freezer. The PpIX fluorescence was negatively affected by repeated light exposure but increased with illumination intensity and exposure time. Though this applied to both healthy and cancer cell lines, and therefore did not statistically improved the differentiation between cell types. This study revealed important experimental settings that need to be carefully considered to benefit from the analytical potential of HAL induced fluorescence when used in technologies for the diagnosis of cancer from body fluids.

usc Refereed/Peer-reviewed Electric fields can induce bond breaking and bond forming, catalyze chemical reactions on surfaces, and change the structure of self-assembled monolayers on electrode surfaces. Here, we study the effect of electric fields supplied either by an electrochemical potential or by conducting atomic force microscopy (C-AFM) on Si-based monolayers. We report that typical monolayers on silicon undergo partial desorption followed by the oxidation of the underneath silicon at +1.5 V vs Ag/AgCl. The monolayer loses 28% of its surface coverage and 55% of its electron transfer rate constant (ket) when +1.5 V electrochemical potential is applied on the Si surface for 10 min. Similarly, a bias voltage of +5 V applied by C-AFM induces complete desorption of the monolayer at specific sites accompanied by an average oxide growth of 2.6 nm when the duration of the bias applied is 8 min. Current-voltage plots progressively change from rectifying, typical of metal-semiconductor junctions, to insulating as the oxide grows. These results define the stability of Si-based organic monolayers toward electric fields and have implication in the design of silicon-based monolayers, molecular electronics devices, and on the interpretation of charge-transfer kinetics across them.

Anodization of titanium is used to form dual scale nanoporous titanium oxide surfaces (NanoTi) that are highly stable, relatively low cost and exhibit unique optoelectronic properties. Due to their high biocompatibility, electrical conductivity and surface area, NanoTi surfaces also promise to be useful electrode materials for biosensors. In this study, we investigated the feasibility of using NanoTi surfaces as a size-selective electrode material for the detection of nano-sized objects. Gold nanoparticles ranging from 16 to 69 nm in diameter were used to model the binding behaviors of bioanalytes, such as enzymes, exosomes and viruses. A size-dependent, steric-like exclusion phenomenon appears to determine the binding location of the nanoparticles within the dual scale nanostructure present on the NanoTi surfaces. Nanoparticles smaller than the pore diameter were observed to bind to ridges between pores, while larger nanoparticles bound onto the pores. The binding events were monitored by Electrochemical Impedance Spectroscopy (EIS), which highlighted that the electrochemical signal measured was dependent on the location of the nanoparticle upon binding. On-pore binding reduced the overall system resistance, while on-ridge binding increased it. These proof-of-concept results indicate that NanoTi surfaces could be used in the development of electrochemical sensors that intrinsically promote the binding of a nano-analyte within a certain size range. Refereed/Peer-reviewed

Simple Summary Prostate cancer is the second most common cancer and the fifth leading cause of cancer death in men worldwide. The current diagnosis methods for prostate cancer are invasive and costly. In particular, digital rectal examination (DRE) or prostate massage adds considerable discomfort to patients, reduces compliance to cancer screening schedules, and raises the cost of the diagnostic procedure. New technologies are urgently needed for the effective and yet noninvasive detection of these conditions. This manuscript describes streamlined biotechnology for the noninvasive detection of prostate cancer from malignant cells shed in urine. For the first time, a whole-cell immunocapture approach combined with photodynamic diagnostic principles is used in a device to detect whole cancer cells from unprocessed patient urine samples collected without prior DRE. Abstract Urine-based biomarkers have shown suitable diagnostic potential for prostate cancer (PCa) detection. Yet, until now, prostatic massage remains required prior to urine sampling. Here, we test a potential diagnostic approach using voided urine collected without prior digital rectal examination (DRE). In this study, we evaluated the diagnostic performance of a microfluidic-based platform that combines the principle of photodynamic diagnostic with immunocapture for the detection of PCa cells. The functionality and sensitivity of this platform were validated using both cultured cells and PCa patient urine samples. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) demonstrated this platform had a detection limit of fewer than 10 cells per 60 µL and successfully validated the presence of a PCa biomarker in the urine of cancer patients without prior DRE. This biosensing platform exhibits a sensitivity of 72.4% and a specificity of 71.4%, in suitable agreement with qRT-PCR data. The results of this study constitute a stepping stone in the future development of noninvasive prostate cancer diagnostic technologies that do not require DRE.

Liquid biopsy targets rare cells that overexpress disease-specific membrane markers and capture these cells via immunoaffinity. The diagnosis efficiency of liquid biopsy can be impaired by the presence of healthy adherent cells also expressing the same biomarkers. Here, we investigated the effect of settling times and rinsing flow rates on the efficiency of EpCAM-based immunocapture using both simulation and experiments with three different cell types. Cell-surface adhesion forces and shear rates were calculated to define the range of rinsing flow rates to test experimentally. Healthy adherent cells did not adhere to blocked immunofunctionalized surfaces within the timeframe of the experiment; however, healthy EpCAM positive cells did bind to the surface to some extent. The greatest difference in capture efficiency was obtained using a high rinsing flow rate of 25 mL/min following 40 min static incubation, indicating that optimizing rinsing flow rates could be a viable option to capture, more specifically, cancer cells overexpressing EpCAM. Refereed/Peer-reviewed

Refereed/Peer-reviewed Dissolving microneedles are a noninvasive transdermal drug delivery platform that offers painless needle-free patient treatment. Current strategies to control the kinetics of drug release from the polymeric microneedle patches consist of adjusting the bulk polymer formulations and/or encapsulating the cargo in controlled delivery vehicles. Instead, in this study, the drug release rates were altered by modifying the surface properties of the microneedles using plasma polymer coatings with tailored properties. The main advantage of this one-step, solvent-free, and scalable method is that it can be applied to any type of microneedles regardless of their drug cargo or bulk material. Octadiene plasma polymer films were found to suppress the burst release effect of otherwise rapidly dissolving microneedles and to reduce the dissolution rate by a factor of four compared to uncoated control patches. The approach presented in this study offers an alternative, highly tunable, and customizable strategy for controlling drug release rate from microneedle patches.

Biomolecules readily and irreversibly bind to plasma deposited Polyoxazoline thin films in physiological conditions. The unique reactivity of these thin films toward antibodies is driving the development of immunosensing platforms for applications in cancer diagnostics. However, in order for these coatings to be used as advanced immunosensors, they need to be incorporated into microfluidic devices that are sealed via plasma bonding. In this work, the thickness, chemistry and reactivity of the polyoxazoline films were assessed following plasma activation. Films deposited from methyl and isopropenyl oxazoline precursors were integrated into spiral microfluidic devices and biofunctionalized with prostate cancer specific antibodies. Using microbeads as model particles, the design of the spiral microfluidic was optimised to enable the size-based isolation of cancer cells. The device was tested with a mixed cell suspension of healthy and malignant prostate cells. The results showed that, following size-specific separation in the spiral, selective capture was achieved on the immunofunctionalised PPOx surface. This proof of concept study demonstrates that plasma deposited polyoxazoline can be used for immunosensing in plasma bonded microfluidic devices. Refereed/Peer-reviewed

Electrochemical immunosensors are an emerging technology for the fast, sensitive, and reliable diagnosis of diseases from bodily fluids. These sensors work by detecting a change in current upon analyte binding to an immuno-functionalized electrode. Current methods of electrode functionalization are lengthy processes involving self-assembled monolayer formation and wet chemistry biofunctionalization. Herein, thin films deposited from the plasma phase of oxazoline precursors are investigated and optimized as an alternative approach for electrode functionalization. The plasma-enabled method has the advantage of being substrate independent and allows the spontaneous binding of biomolecules in physiological buffer. Surface sensitive analysis techniques are employed to characterize the thickness, reactivity, and stability of the thin films before investigating their electrochemical properties on indium tin oxide and gold electrodes including the feasibility to reduce charge transfer resistance with gold nanoparticles. Last, these films are employed to develop an immunosensor for the detection of free epithelial cell adhesion molecule with a limit of detection of 8.7 ng mL−1 Refereed/Peer-reviewed

Bladder cancer is common and has one of the highest recurrence rates. Cystoscopy, the current gold standard diagnosis approach, has recently benefited from the introduction of blue light assisted photodynamic diagnostic (PDD). While blue light cystoscopy improves diagnostic sensitivity, it remains a costly and invasive approach. Here, we present a microfluidic-based platform for non-invasive diagnosis which combines the principle of PDD with whole cell immunocapture technology to detect bladder cancer cells shed in patient urine ex vivo. Initially, we demonstrate with model cell lines that our non-invasive approach achieves highly specific capture rates of bladder cancer cells based on their Epithelial Cell Adhesion Molecule expression (>90%) and detection by the intensity levels of Hexaminolevulinic Acid-induced Protoporphyrin IX fluorescence. Then, we show in a pilot study that the biosensor platform successfully discriminates histopathologically diagnosed cancer patients (n = 10) from non-cancer controls (n = 25). Our platform can support the development of a novel non-invasive diagnostic device for post treatment surveillance in patients with bladder cancer and cancer detection in patients with suspected bladder cancer Refereed/Peer-reviewed

Blue light cystoscopy (BLC) is the most recent clinical approach in the detection and diagnosis of bladder cancer, a common type of cancer with a high rate of recurrence. Representing a significant advance over previous approaches, this photodynamic diagnostic technique uses a photosensitiser prodrug as an adjunct to white light cystoscopy to enhance the in vivo detection of malignant tissues in the bladder based on their distinctive fluorescence. Whilst it does improve detection rates, BLC remains an invasive and costly procedure. Meanwhile, a variety of noninvasive urine detection methods and related microdevices have been developed, none of which have yet entered routine clinical use due to unsatisfactory sensitivity. Following a brief description of the current approaches and their limitations, we provide here a systematic review of a newer niche research aiming to develop a noninvasive adaptation of photodynamic diagnosis. The research to date surrounding the ex situ use of photosensitiser prodrugs for urinary diagnosis of bladder cancer is also discussed. Refereed/Peer-reviewed

Prostate cancer is the second most common cancer in men and the second leading cause of male cancer deaths. The current blood test for detecting prostate cancers measures prostate-specific antigen. It has many limitations including a very high rate of false positives. Herein, prostate-specific membrane antigen (PSMA) based immunocapture and hexaminolevulinate (HAL) based photodetection are integrated into a new diagnostic device designed to selectively identify whole prostate cancer cells from voided urine with the aim of providing an accurate noninvasive alternative to current diagnosis methods. Prestained, prostate cancer cells spiked in urine samples at concentrations ranging from 1500 to 2000 cells/ml were captured with 89% sensitivity and 95% specificity. HAL, a cancer specific photosensitizer, was then used to circumvent the need for prestaining. Optimum HAL incubation conditions were identified (50 μM at 37 °C for 2 h) where the mean HAL-induced fluorescence intensity of LNCaP cells was three times that of healthy PNT2 cells, thus providing an independent way to discriminate captured cancer cells from background metabolites. Combining anti-PSMA immunocapture with HAL-induced fluorescent detection, 86% sensitivity and 88% selectivity were achieved, thereby proving the validity of the dual-method for the selective photospecific detection of prostate cancer cells Refereed/Peer-reviewed

Polyoxazolines arise as a promising new class of polymers for biomedical applications, but creating oxzoline-based coatings via conventional methods is challenging. Herein, nanoscale polyoxazoline coatings were generated via a single step plasma deposition process. The effects of plasma deposition conditions on the film stability, structure and chemical group density were investigated. Detailed examination of the physical and chemical properties of plasma deposited polyoxazoline via XPS, FTIR, contact angle and ellipsometry unravels the complex functionality of the films. Partial retention of the oxazoline ring facilitates a covalent reaction with the carboxylic acid groups present on nanoparticles and biomolecules. Surface bound proteins effectively retain their bioactivity, therefore a vast range of potential applications unlocks for plasma deposited polyoxazoline coatings in the field of biosensing, medical arrays and diagnosis. Refereed/Peer-reviewed

The nature of the protein corona forming on biomaterial surfaces can affect the performance of implanted devices. This study investigated the role of surface chemistry and wettability on human serum-derived protein corona formation on biomaterial surfaces and the subsequent effects on the cellular innate immune response. Plasma polymerization, a substrate-independent technique, was employed to create nanothin coatings with four specific chemical functionalities and a spectrum of surface charges and wettability. The amount and type of protein adsorbed was strongly influenced by surface chemistry and wettability but did not show any dependence on surface charge. An enhanced adsorption of the dysopsonin albumin was observed on hydrophilic carboxyl surfaces while high opsonin IgG2 adsorption was seen on hydrophobic hydrocarbon surfaces. This in turn led to a distinct immune response from macrophages; hydrophilic surfaces drove greater expression of anti-inflammatory cytokines by macrophages, whilst surface hydrophobicity caused increased production of proinflammatory signaling molecules. These findings map out a unique relationship between surface chemistry, hydrophobicity, protein corona formation, and subsequent cellular innate immune responses; the potential outcomes of these studies may be employed to tailor biomaterial surface modifications, to modulate serum protein adsorption and to achieve the desirable innate immune response to implanted biomaterials and devices. usc Refereed/Peer-reviewed

usc Kidney disease is now recognized as a global health problem and is associated with increased morbidity and mortality, along with high economic costs. To develop new treatments for ameliorating kidney injury and preventing disease progression, there is a need for appropriate renal culture systems for screening novel drugs and investigating the cellular mechanisms underlying renal pathogenesis. There is a need for in vitro culture systems that promote the growth and differentiation of specialized renal cell types. In this work, we have used plasma polymerization technology to generate gradients of chemical functional groups to explore whether specific concentrations of these functional groups can direct the differentiation of mouse kidney-derived stem cells into specialized renal cell types. We found that amine-rich (−NH2) allylamine-based plasma-polymerized coatings could promote differentiation into podocyte-like cells, whereas methyl-rich (CH3) 1,7-octadiene-based coatings promoted differentiation into proximal tubule-like cells (PTC). Importantly, the PT-like cells generated on the substrates expressed the marker megalin and were able to endocytose albumin, indicating that the cells were functional. Refereed/Peer-reviewed

The development of suitable biomaterials is key to the progress of biomedical engineering. Plasma deposition is a versatile and waste free technique that can be used to produce surfaces with well denied chemical and physical properties. In this mini-review we show how well-char-acterised plasma deposited organic films have been used to screen and identify optimum substrate properties for several different biomedical applications. By providing as an example the plasma deposited poly oxazolines, we demonstrate the generation of advances biomaterial surfaces capable of limiting biofilm formation, guiding stem cell differentiation and even sensing cancer cells in urine. Refereed/Peer-reviewed

The gold standard to detect bladder cancer, cystoscopy, is an invasive procedure requiring ambulant hospitalization, thus presenting an obstacle for routine diagnosis. We aim to develop a noninvasive detection method as an alternative that selectively captures shed cancer cells in the patient’s urine via surface-immobilized anti-EpCAM antibody. However, the urine sample storage conditions prior to analysis affect the subsequent cancer cell capture rates by the device. In this study, we investigate the capture rates of HT1197 and HT1376 bladder cancer cells in different media (fresh and aged urine as well as PBS) and storage temperatures prior to analysis (37 and 4 °C) as well as in the presence of adjuvants in the medias (free antibodies and cell debris). Capture efficiencies decreased in as little as 1 h of the sample being incubated at 37 °C in all media studied here. Furthermore, cell debris played a strong part in reducing the capture efficiency. From the data, we conclude that storing the sample at 4 °C resulted in the best capture efficiency if storage of more than 1 h was required, which gave valuable insights for this sensor’s translation from laboratory to real-world applications. usc Refereed/Peer-reviewed

Wound infections arising from bacterial contamination and colonisation are of substantial burden to healthcare. Currently, bandages are used to merely provide wounds with physical barriers to bacteria, however they quickly become saturated and ineffective. Silver containing wound dressings have gained commercial and scientific attention as a potential solution to the problem of wound infections. In this work, we compare the antibacterial efficacy of recently patented silver nanoparticle loaded plasma polymer film technology and a commercially available GranuFoam Silver® silver-coated wound dressings. The silver nanoparticle loaded foams contained lower amount of elemental silver than the commercially available wound dressings but both silver-loaded foams had comparable antibacterial capacity. Furthermore, the silver nanoparticle loaded foams had greater hydrophilicity which may be beneficial in applications. Collectively, the results demonstrate that the nanoparticle loaded plasma polymer coating can be used on medical devices such as wound dressings with similar efficacy to existing products. Refereed/Peer-reviewed

Infections caused by the bacterial colonization of medical devices are a substantial problem to patients and healthcare. Biopassive polyoxazoline coatings are attracting attention in the biomedical field as one of the potential solutions to this problem. Here, we present an original and swift way to produce plasma-deposited oxazoline-based films for antifouling applications. The films developed via the plasma deposition of 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline have tunable thickness and surface properties. Diverse film chemistries were achieved by tuning and optimizing the deposition conditions. Human-derived fibroblasts were used to confirm the biocompatibility of oxazoline derived coatings. The capacity of the coatings to resist biofilm attachment was studied as a function of deposition power and mode (i.e., continuous wave or pulsed) and precursor flow rates for both 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline. After careful tuning of the deposition parameters films having the capacity to resist biofilm formation by more than 90% were achieved. The substrate-independent and customizable properties of the new generation of plasma deposited oxazoline thin films developed in this work make them attractive candidates for the coating of medical devices and other applications where bacteria surface colonization and biofilm formation is an issue. Refereed/Peer-reviewed

Plasma polymers derived from oxazoline precursors present a range of versatile properties that is fueling their use as biomaterials. However, coatings deposited from commonly used methyl and ethyl oxazoline precursors can be sensitive to the plasma deposition conditions. In this work, we used various spectroscopic methods (ellipsometry, x-ray photoelectron spectroscopy, and time of flight secondary ion mass spectrometry) and cell viability assays to evaluate the transferability of deposition conditions from the original plasma reactor developed by Griesser to a new wider, reactor designed for upscaled biosensors applications. The physicochemical properties, reactivity, and biocompatibility of films deposited from 2-isopropenyl-2-oxazoline were investigated. Thanks to the availability of an unsaturated pendant group, the coatings obtained from this oxazoline precursor are more stable and reproducible over a range of deposition conditions while retaining reactivity toward ligands and biomolecules. This study identified films deposited at 20 W and 0.012 mbar working pressure as being the best suited for biosensor applications. Refereed/Peer-reviewed

Photodynamic diagnosis and therapy have emerged as a promising tool in oncology. Using the visible fluorescence from photosensitisers excited by light, clinicians can both identify and treat tumour cells in situ. Protoporphyrin IX, produced in the penultimate step of the haem synthesis pathway, is a naturally occurring photosensitiser that visibly fluoresces when exposed to light. This fluorescence is enhanced considerably by the exogenous administration of the substrate 5-aminolaevulinic acid (5-ALA). Significantly, 5-ALA-induced protoporphyrin IX accumulates preferentially in cancer cells, and this enhanced fluorescence has been harnessed for the detection andphotodynamic treatment of brain, skin and bladder tumours. However, surprisingly little is known about the mechanistic basis for this phenomenon. This review focuses on alterations in the haem pathway in cancer and considers the unique features of the cancer environment, such as altered glucose metabolism, oncogenic mutations and hypoxia, and their potential effects on the protoporphyrin IXphenomenon. A better understanding of why cancer cells fluoresce with 5-ALA would improve its use in cancer diagnostics and therapies. Refereed/Peer-reviewed

Surface nanoengineering is a valuable tool to create materials with sophisticated properties required to address unmet needs in fields such as medicine, biology or energy. This study examines the dependence of nanoparticle immobilization as a function of surface amine group density. The concentration of surface amine groups was tuned using gradients deposited from the plasma phase of allylamine and octadiene (pp-AA/OD) precursors mixtures. Silver nanoparticles capped with carboxylic acid groups (COOH-AgNPs) were used to interrogate the effect of primary amine (−NH2) surface density on nanoparticle's electrostatic immobilization onto freshly made and aged plasma polymer films. An increase in amine group density could be correlated with greater number of functionalized silver nanoparticles bound to the surface. In addition, the pp-AA/OD surface charge and nanoparticle binding density could be controlled via pH of the AgNPs colloidal solution. The results suggest that pp-AA/OD plasma polymer films are suitable platforms for implementing advanced nanoengineered materials that could be used in many advanced applications, ranging from medicine to sensing and electronics. Refereed/Peer-reviewed

Protein adsorption to biomaterials is critical in determining their suitability for specific applications, such as implants or biosensors. Here, we show that surface nanoroughness can be tailored to control the covalent binding of proteins to plasma-deposited polyoxazoline (PPOx). Nanoengineered surfaces were created by immobilizing gold nanoparticles varying in size and surface density on PPOx films. To keep the surface chemistry consistent while preserving the nanotopography, all substrates were overcoated with a nanothin PPOx film. Bovine serum albumin was chosen to study protein interactions with the nanoengineered surfaces. The results demonstrate that the amount of protein bound to the surface is not directly correlated with the increase in surface area. Instead, it is determined by nanotopography-induced geometric effects and surface wettability. A densely packed array of 16 and 38 nm nanoparticles hinders protein adsorption compared to smooth PPOx substrates, while it increases for 68 nm nanoparticles. These adaptable surfaces could be used for designing biomaterials where proteins adsorption is or is not desirable. Refereed/Peer-reviewed

Plasma deposited polyoxazoline thin films share many valuable properties with polyoxazoline prepared via conventional organic chemistry; they are biocompatible, non-cytotoxic and low fouling. What is more, they bind biomolecules covalently, support cell adhesion, and are generated in a solvent free, single step process. Here, we show that the secret for plasma deposited polyoxazolines’ unique set of properties lies in both the chemical fragmentation processes occurring in the plasma phase itself and the recombination events subsequently occurring at the plasma-activated surface. In situ plasma mass spectroscopy was used to elucidate the complex composition of the oxazoline plasma phase at nominal powers ranging from 2 to 50W. This confirmed the stability of the un-opened monomer, but also revealed the formation of nitrile, isocyanate, and imine species. In correlation with post-plasma surface characterization data, the mass spectroscopy results indicate that reactive functional groups were plasma-generate...

Stem cell-based therapies are emerging as a potent new approach to treat a variety of diseases. This chapter is focused on the application and potential of plasma-assisted material modification in stem cells culture substrates and therapies. The effect of substrate chemical and physical properties achieved using plasma-coating methods on the fate of stem cells is reviewed. In particular, plasma-assisted methods to produce tailored surface chemistries, controlled topography and stiffness, surface gradient substrates, and modify 3D structures are explained together with their significance in addressing challenges faced in conventional stem cell culture. Refereed/Peer-reviewed

usc We report on the use of helium plasma jet for plasma polymerisation of 2‐methyl‐2‐oxazoline (OX) on heated silicon substrates. The X‐ray photo electron spectroscopy (XPS) characterisation shows a substantial improvement in film stability in buffer solution when depositing at temperatures above 50°C. Principal component analysis of the time‐of‐flight–secondary ion mass spectrometry data shows excellent correlation with the XPS results, providing insights into the degree of crosslinking in the plasma coatings as a function of substrate temperature. Atomic force microscopy images showed the topography of OX plasma polymer coatings deposited at 80°C and 120°C to be smoother with lower surface roughness values compared to those produced at 50°C. Finally, an 80% reduction in the adhesion of Staphylococcus epidermidis is achieved at the centre of the plasma coatings deposited at 120°C. Refereed/Peer-reviewed

usc

The surface chemistry and topography of biomaterials regulate the adhesion and growth of microorganisms in ways that are still poorly understood. Silicon nanograss structures prepared via inductively coupled plasma etching were coated with plasma deposited nanometer-thin polymeric films to produce substrates with controlled topography and defined surface chemistry. The influence of surface properties on Staphylococcus aureus proliferation is demonstrated and explained in terms of nanograss substrate wetting behaviour. With the combination of the nanograss topography; hydrophilic plasma polymer coatings enhanced antimicrobial activity while hydrophobic coatings reduced it. This study advances the understanding of the effects of surface wettability on the bactericidal properties of reactive nano-engineered surfaces. Refereed/Peer-reviewed

Hypothesis Silver nanoparticles (AgNPs) have emerged as a powerful weapon against antibiotic resistant microorganisms. However, most conventional AgNPs syntheses require the use of hazardous chemicals and generate toxic organic waste. Hence, in recent year’s, plant derived and biomolecule based synthetics have has gained much attention. Cacao has been used for years for its medicinal benefits and contains a powerful reducing agent - oxalic acid. We hypothesized that, due to the presence of oxalic acid, cacao extract is capable of reducing silver nitrate (AgNO 3 ) to produce AgNPs. Experiments In this study, AgNPs were synthesized by using natural cacao extract as a reducing and stabilizing agent. The reaction temperature, time and reactant molarity were varied to optimize the synthesis yield. Findings UV–visible spectroscopy (UV–vis), dynamic light scattering (DLS) and transmission electron microscopy (TEM) characterization demonstrated that the synthesized AgNPs were spherical particles ranging in size from 35 to 42.5 nm. The synthesized AgNPs showed significant antibacterial activity against clinically relevant pathogens such as Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus and Staphylococcus epidermidis . Importantly, these green AgNPs are not cytotoxic to human dermal fibroblasts (HDFs) at concentrations below 32 μg/ml. We conclude that cacao-based synthesis is a reproducible and sustainable method for the generation of stable antimicrobial silver nanoparticles with low cytotoxicity to human cells. The AgNPs synthesized in this work have promising properties for applications in the biomedical field.

The time dependent alignment of exfoliated nontronite dispersions subjected to moderate magnetic field strengths (B < 0.8 T) is investigated. The chemical and physical properties of nontronite are thoroughly characterised as well as the phase behaviour of its aqueous dispersions at concentrations between 0.2 and 0.7. vol.%. The degree of nontronite alignment is associated with a birefringent light glow which increases with magnetic field strength, time and clay mineral concentration. Theoretical modelling indicates that the experimentally determined alignment kinetics have a characteristic timescale best described by a probability distribution. These findings are of importance for designing the optical, mechanical and barrier properties of clay polymer nanocomposites. Refereed/Peer-reviewed